p53-dependent induction of prostate cancer cell senescence by the PIM1 protein kinase.

Molecular Cancer Research : MCR
Marina ZemskovaAndrew S Kraft

Abstract

The PIM family of serine threonine protein kinases plays an important role in regulating both the growth and transformation of malignant cells. However, in a cell line-dependent manner, overexpression of PIM1 can inhibit cell and tumor growth. In 22Rv1 human prostate cells, but not in Du145 or RWPE-2, PIM1 overexpression was associated with marked increases in cellular senescence, as shown by changes in the levels of beta-galactosidase (SA-beta-Gal), p21, interleukin (IL)-6 and IL-8 mRNA and protein. During early cell passages, PIM1 induced cellular polyploidy. As the passage number increased, markers of DNA damage, including the level of gammaH2AX and CHK2 phosphorylation, were seen. Coincident with these DNA damage markers, the level of p53 protein and genes transcriptionally activated by p53, such as p21, TP53INP1, and DDIT4, increased. In these 22Rv1 cells, the induction of p53 protein was associated not only with senescence but also with a significant level of apoptosis. The importance of the p53 pathway to PIM1-driven cellular senescence was further shown by the observation that expression of dominant-negative p53 or shRNA targeting p21 blocked the PIM1-induced changes in the DNA damage response and increases in SA-beta-G...Continue Reading

References

Oct 1, 1989·Analytical Biochemistry·W KuengU Eppenberger
Nov 1, 1989·Proceedings of the National Academy of Sciences of the United States of America·R AmsonA Telerman
May 9, 1995·Proceedings of the National Academy of Sciences of the United States of America·Q ChenB N Ames
Dec 24, 1998·Toxicologic Pathology·C F van KreijlR D Storer
Sep 6, 2000·Proceedings of the National Academy of Sciences of the United States of America·S MatsuokaS J Elledge
Aug 21, 2001·Molecular Cell·S OkamuraY Nakamura
Aug 24, 2001·Nature·S M DhanasekaranA M Chinnaiyan
Jul 12, 2002·Chromosoma·Nandini BhattacharyaNancy S Magnuson
Dec 17, 2002·Journal of Cell Science·Jennifer S Michaelson, Philip Leder
Apr 3, 2003·Biochemical and Biophysical Research Communications·Bálint TomborZoltán N Oltvai
Jul 23, 2003·The Biochemical Journal·Elvira CrescenziHugh J M Brady
Oct 1, 2003·The Prostate·Adrie van BokhovenM Scott Lucia
Oct 3, 2003·Cancer Cell·Katharine Ellwood-YenCharles L Sawyers
Jul 21, 2004·The Prostate·Alexander ValdmanLars Egevad
Sep 2, 2004·The Journal of Biological Chemistry·Monica GostissaGiannino Del Sal
Nov 6, 2004·The Journal of Immunology : Official Journal of the American Association of Immunologists·Barbara A StoutPaul J Bertics
Dec 24, 2004·The EMBO Journal·Alfonso CatalanoAntonio Procopio
Mar 31, 2005·Molecular Cancer Research : MCR·Kate Petersen ShayNancy S Magnuson
Jun 14, 2005·Cancer Cell·Goberdhan P Dimri
Aug 27, 2005·Molecular Cancer Research : MCR·Wei Wei ChenAndrew S Kraft
Oct 14, 2005·The Journal of Biological Chemistry·Meejeon RohSarki A Abdulkadir
Mar 1, 2006·Journal of Clinical Pathology·T L CibullL Cheng
Dec 1, 2006·Nature·Raffaella Di MiccoFabrizio d'Adda di Fagagna
Mar 1, 2007·Blood·Yu-Long HuHugh Jeffrey Lawrence
Aug 3, 2007·Cell Cycle·Frédérick A Mallette, Gerardo Ferbeyre
Sep 19, 2007·Laboratory Investigation; a Journal of Technical Methods and Pathology·Jeremy C WallentineMegan S Lim

❮ Previous
Next ❯

Citations

Nov 19, 2010·Cancer Research·Jin H SongAndrew S Kraft
May 7, 2014·Future Oncology·Jianwei XuYupei Zhao
Jan 15, 2015·Future Medicinal Chemistry·Bich Thuy LeShudong Wang
Mar 6, 2012·Expert Opinion on Investigational Drugs·Anna Lena MerkelMatthias Ocker
Oct 9, 2012·Biochemical Pharmacology·Carmen Blanco-Aparicio, Amancio Carnero
Apr 12, 2013·Medicinal Research Reviews·Maja Narlik-GrassowAmancio Carnero
Nov 20, 2019·Proteomics·Marie-Veronique Clement, Le Luo
Nov 3, 2017·Scientific Reports·Po-Shuan HuangKwang-Huei Lin
Apr 29, 2018·Cancer Research·Eun Mi KimHong-Duck Um
Mar 18, 2021·Seminars in Cancer Biology·Halina WasClaudine Kieda
May 16, 2018·Biochemical and Biophysical Research Communications·Xiangwen ZhanWenhua Yu
May 8, 2021·Aging·Pianpian HuangBenling Qi
Aug 11, 2021·The Journal of Pathology. Clinical Research·Antonin BouroumeauHervé Sartelet

❮ Previous
Next ❯

Related Concepts

Related Feeds

Apoptosis in Cancer

Apoptosis is an important mechanism in cancer. By evading apoptosis, tumors can continue to grow without regulation and metastasize systemically. Many therapies are evaluating the use of pro-apoptotic activation to eliminate cancer growth. Here is the latest research on apoptosis in cancer.

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis